ORCID
https://orcid.org/https://orcid.org/0000-0003-3229-4181
Date of Award
2024
Document Type
Dissertation
Degree Name
Philosophy (Ph.D)
Department
Pharmaceutical Sciences
First Advisor
Carlos Sanhueza Chavez
Second Advisor
Vijaya Korlipara
Third Advisor
Tanaji Talele
Abstract
Leishmaniasis is a neglected tropical disease caused by the protozoan parasite of the genus Leishmania. Presently no vaccine against Leishmaniasis is available, so there is a need for new anti-leishmanial treatments, including an effective preventive vaccine. We focus on developing vaccine candidates based on leishmania’s cell surface carbohydrate antigens. Saccharides heavily envelop the cell surface of Leishmania, lipophosphoglycan (LPG) becoming a significant glycan in most leishmania species. Its intrinsic antigenicity makes this polysaccharide a useful target for developing conjugated vaccine candidates against all leishmaniasis variants. In this report, we present our progress towards the synthesis of the fragments of LPG present in Leishmania donovani, the causative agent of visceral leishmaniasis (VL) for its further utilization in the glycoconjugate vaccine candidate. Two clickable forms of Galβ(1,4)Man, mainly O-glycoside and phospho-glycoside moieties, were synthesized to facilitate their conjugation to protein carriers. These derivatives were synthesized to support subsequent investigations into immunological responses and antibody-binding properties. Moreover, capping tetrasaccharide was synthesized successfully from Galman core using orthoester strategy. To finalize the synthesis of the target Leishmania donovani LPG fragment, we linked the capping tetrasaccharide with the GalMan repeating unit via a phosphodiester bond
Recommended Citation
Budhathoki, Dipesh, "SYNTHESIS OF LEISHMANIA SPP ANTIGENS FOR THE DEVELOPMENT OF VACCINE CANDIDATES" (2024). Theses and Dissertations. 829.
https://scholar.stjohns.edu/theses_dissertations/829